immunotherapy with chemotherapy and chemoradiation for advanced squamous cancer of nasal cavity / paranasal sinuses (i-napa)

Conditions: Squamous Cell Carcinoma; the Nasal Cavity; Paranasal Sinuses

Summary: this is a single arm phase ii study that will evaluate the combination of pembrolizumab, docetaxel, and cisplatin or carboplatin (pdc) as single treatment modality in patients with stage ii-ivb (t2-4, any n, m0) squamous cell carcinoma of the nasal cavity/paranasal sinuses (pns scc).

primary objective -increase overall response rate (orr), following pembrolizumab combined with induction chemotherapy prior to radiation, from historical 60% with induction chemotherapy alone to 80%. secondary objective * improve the following efficacy endpoints relative to historical results with chemotherapy alone: progression free survival (pfs), overall survival (os), organ \[orbital, maxillary, cranial\] preservation rate (opr), and locoregional failure (lrf). * to determine safety and tolerability of pembrolizumab combined with induction chemotherapy and chemoradiation in patients with pns scc. * correlate immune phenotype in tumors and blood, including t cell infiltration and pd-l1 status, with treatment outcomes.

Eligibility criteria:
inclusion criteria: * male/female participants who are at least 18 years of age on the day of signing informed consent with newly diagnosed, previously untreated, histologically and/or cytologically confirmed diagnosis of stage ii-ivb pns scc will be enrolled in this study. * male participants: a male participant must agree to use a contraception as detailed in appendix 3 of this protocol during the treatment period and for at least 150 days after the last dose of study treatment and refrain from donating sperm during this period. -female participants: a female participant is eligible to participate if she is not pregnant (see appendix 3), not breastfeeding, and at least one of the following conditions applies: 1. not a woman of childbearing potential (wocbp) as defined in appendix 3 or 2. a wocbp who agrees to follow the contraceptive guidance in appendix 3 during the treatment period and for at least 150 days after the last dose of study treatment. * the participant (or legally acceptable representative if applicable) provides written informed consent for the trial. * have measurable disease based on recist 1.1. * have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. formalin-fixed, paraffin embedded (ffpe) tissue blocks are preferred to slides. newly obtained biopsies are preferred to archived tissue. * have an eastern cooperative oncology group (ecog) performance status of 0 to 1. have adequate organ function as defined in the following table (table 1). blood must be collected within 14 days prior to the start of study treatment. exclusion criteria: * a wocbp who has a positive urine pregnancy test within 72 hours prior to treatment (see appendix 3). if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. * has received prior therapy with an anti-pd-1, anti-pd-l1, or anti pd l2 agent or with an agent directed to another stimulatory or co-inhibitory t-cell receptor (eg, ctla-4, ox 40, cd137). * patients must not have received prior systemic anti-cancer therapy including investigational agents or radiation therapy for pns scc but could have received treatment for prior cancers if greater than 2 years (refer to item 8 for further details).